Amarin Corporation plc (NASDAQ:AMRN) today announced an exploratory post hoc sub-analysis of REDUCE-IT serum samples that found statin-treated patients allocated to icosapent ethyl (IPE) had limited differences in certain lipid and inflammatory biomarkers compared with statin-treated patients allocated to mineral oil placebo. These findings are consistent with prior reported data and support previous analyses that demonstrated the majority of benefit from IPE was from achieved eicosapentaenoic acid (EPA) levels in REDUCE-IT. This sub-analysis was published online today in the journal Circulation.
In the landmark REDUCE-IT cardiovascular outcomes study, IPE achieved 25 percent relative risk reduction of major adverse cardiovascular events (MACE, 5-point composite endpoint: cardiovascular death, non-fatal heart attack, non-fatal stroke, coronary revascularization, or unstable angina). This also included relative risk reductions of 31 percent, 28 percent and 20 percent in heart attacks, strokes and cardiovascular deaths, respectively. As previously presented, the only marker that seems to have strong association with reductions in MACE from the REDUCE-IT study is serum EPA levels; these data were previously presented at the American College of Cardiology Scientific Sessions in 2020.i
“Regardless of biomarker pathway, effects were small on an absolute scale for both icosapent ethyl and for placebo, and changes in values were mostly below the limits of quantification in this exploratory sub-analysis,” said Deepak L. Bhatt, M.D., M.P.H., Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School, principal investigator of REDUCE-IT and co-author of the biomarker sub-analysis. “While the mechanisms of action contributing to the reduction of cardiovascular events with icosapent ethyl are not completely understood and are likely multi-factorial, previous studies have clearly demonstrated the anti-inflammatory effects of EPA. The current analysis of REDUCE-IT finds a difference in inflammatory markers between icosapent ethyl and placebo, however, the absolute magnitude of these differences is too small to explain the substantial reduction in clinical events seen in the REDUCE-IT trial, which is most likely due to the approximate 400% increase in EPA levels.”
